Liposomes are composed of phospholipids that constitute the cell membranes of organisms, they have high biocompatibility, and they can deliver drugs and active ingredients while protecting them from degrading enzymes in vivo. Accordingly, liposomes have gained attention as useful tools for drug delivery systems.
Meanwhile, RNAi molecules that induce RNA interference (hereafter referred to as “RNAi”) have gained attention as useful tools for tumor treatment and other purposes, and a wide variety of RNAi molecules that are capable of tumor growth inhibition have been developed. In addition, a method of using complexes composed of RNAi molecules and lipid mixtures (i.e., lipoplexes) to deliver RNAi molecules as active ingredients to tumor cells have been developed (Qixin Leng et al., Drug Future, September 2009; 34 (9): 721; Sherry Y., Wu et al., The AAPS Journal, Vol. 11, No. 4, December 2009; and B. Ozpolat et al., Journal of Internal Medicine 267; 44-53, 2009).
In the past, the present inventors developed RNAi molecules targeting thymidylate synthases (hereafter referred to as “TS”), which are involved with tumor growth (WO 2010/113844). They reported that delivery of such RNAi molecules to the tumors via, for example, intravenous administration with the use of complexes (lipoplexes) included in a cationic lipid mixture of a given formulation would make it possible to inhibit the growth of tumors showing TS expression. They also reported that the use of such lipoplexes in combination with chemotherapeutic agents would result in the improvement of tumor-targeting efficiency as well as the improvement of antitumor effects of RNAi molecules to a significant extent (WO 2012/161196).